JPH0623130B2 - Method for producing α-keto acid - Google Patents
Method for producing α-keto acidInfo
- Publication number
- JPH0623130B2 JPH0623130B2 JP59141330A JP14133084A JPH0623130B2 JP H0623130 B2 JPH0623130 B2 JP H0623130B2 JP 59141330 A JP59141330 A JP 59141330A JP 14133084 A JP14133084 A JP 14133084A JP H0623130 B2 JPH0623130 B2 JP H0623130B2
- Authority
- JP
- Japan
- Prior art keywords
- hydantoin
- keto acid
- producing
- reaction
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Description
【発明の詳細な説明】 （産業上の利用分野） 本発明はα−ケト酸の改良された製造方法に関するもの
である。TECHNICAL FIELD The present invention relates to an improved method for producing α-keto acids.
α−ケト酸は有機合成化学上のみならず生化学上きわめ
て重要な化合物であり、近年バイオテクノロジーの進歩
と共に、食品添加剤及び農医薬に使用されるＬ−α−ア
ミノ酸の出発原料として重要な位置を占めるに至ってい
る。α-Keto acids are extremely important compounds not only in synthetic organic chemistry but also in biochemistry, and with the progress of biotechnology in recent years, they are important as starting materials for L-α-amino acids used in food additives and agricultural medicine. It has reached the position.
（従来技術とその問題点） α−ケト酸を製造する方法は種々検討されているが、本
発明のように５−（置換アリ−リデン）ヒダントインを
加水分解してα−ケト酸を製造する方法の提案は極めて
少ない。(Prior Art and Its Problems) Various methods for producing α-keto acids have been studied, but as in the present invention, 5- (substituted aryl-lidene) hydantoin is hydrolyzed to produce α-keto acids. There are very few method proposals.
例えば、Monatsh92，343(1961)には５−（置換アリ−リ
デン）ヒダントインとして５−（ベンジリデン）ヒダン
トインを使用し、29.4モル倍の苛性ソーダを用い、油浴
温度170〜180℃で反応混合物の沸点において加水分解を
行ない、６０％の収率でフェニルピルビン酸を得てい
る。しかし、この方法に記載されている苛性ソーダの使
用量で沸点において加水分解させる場合、収率が非常に
低く、ベンズアルデヒド、安息香酸、ヒダントイン酸等
の多くの副生成物が生成し、かつ、反応混合物中の過剰
の苛性ソーダを同量の鉱酸によって中和するため、フェ
ニルピルビン酸を回収精製するのに多大の労力と時間を
要し、経済的に好ましくない。For example, in Monatsh 92, 343 (1961), 5- (benzylidene) hydantoin is used as 5- (substituted arylidene) hydantoin, 29.4 mol times of caustic soda is used, and the boiling point of the reaction mixture at an oil bath temperature of 170 to 180 ° C. Hydrolysis was performed to obtain phenylpyruvic acid in a yield of 60%. However, when hydrolyzing at the boiling point with the amount of caustic soda described in this method, the yield is very low, many by-products such as benzaldehyde, benzoic acid, hydantoic acid are produced, and the reaction mixture Since an excessive amount of caustic soda is neutralized with the same amount of mineral acid, it takes a lot of labor and time to collect and purify phenylpyruvic acid, which is not economically preferable.
（問題を解決するための手段） 本発明者らは、このような従来技術にみられる欠点を是
正し、高収率でα−ケト酸を経済的に製造する方法につ
いて鋭意検討した結果、使用アルカリ量を1.5〜2.5モル
倍とし、反応温度を８０〜110℃の狭い範囲に制限する
ことにより、前記の目的が達成されることを見出し本発
明に到達した。(Means for Solving the Problem) The present inventors have made diligent studies on a method for economically producing α-keto acid with a high yield by correcting the drawbacks found in such a conventional technique, and as a result, use thereof. The inventors have found that the above object can be achieved by limiting the amount of alkali to 1.5 to 2.5 mol times and limiting the reaction temperature to a narrow range of 80 to 110 ° C.
すなわち、本発明は５−（置換アリ−リデン）ヒダント
インを1.5〜2.5モル倍のアルカリ金属水酸化物の存在下
８０〜110℃で加水分解することを特徴とするα−ケト
酸の製造方法である。本発明の方法で用いられる原料
は、一般式（Ｉ） （式中、Ｒ1およびＲ2は、水素原子、ハロゲン原子、水
酸基または炭素数１〜３のアルキル基を示し、互いに同
一または異ってもよい）で表わされる５−（置換アリ−
リデン）ヒダントインである。That is, the present invention provides a method for producing an α-keto acid, which comprises hydrolyzing 5- (substituted aryl-lidene) hydantoin at 80 to 110 ° C. in the presence of 1.5 to 2.5 mole times of alkali metal hydroxide. is there. The raw material used in the method of the present invention has the general formula (I) (In the formula, R 1 and R 2 represent a hydrogen atom, a halogen atom, a hydroxyl group or an alkyl group having 1 to 3 carbon atoms, and may be the same or different from each other) 5- (substituted ary-
Redden) It is hydantoin.
これらの５−（置換アリ−リデン）ヒダントインは、例
えば、ヒダントインと置換ベンズアルデヒドを水−モノ
アルカノ−ルアミン系で縮合させる米国特許2,861,079
号、あるいは、酢酸ソーダー酢酸系で縮合されるMonats
h92、352(1961)等の記載方法により得られる。These 5- (substituted aryl-lidene) hydantoins are described, for example, in US Pat. No. 2,861,079, in which hydantoin and a substituted benzaldehyde are condensed with a water-monoalkanolamine system.
No. or Monats condensed with sodium acetate acetic acid system
It can be obtained by the method described in h92, 352 (1961) and the like.
具体的には、５−（ベンジリデン）ヒダントイン、ある
いは、上記の一般式（Ｉ）におけるＲ1とＲ2で示される
基が２−ヒドロキシ、３−ヒドロキシ、４−ヒドロキ
シ、2・4−ジヒドロキシ、2・5−ジヒドロキシ、3・4−ジ
ヒドロキシ、２−メチル、３−メチル、４−メチル、２
−エチル、３−エチル、４−エチル、２−プロピル、３
−プロピル、４−プロピル、２−メトキシ、３−メトキ
シ、４−メトキシ、５−メチル−２−ヒドロキシ、３−
メチル−４−ヒドロキシ、２−ヒドロキシ−３−メトキ
シ、３−メトキシ−４−ヒドロキシ、３−ヒドロキシ−
４−メトキシ、2・4−ジメトキシ、3・4−ジメトキシ、3・
5−ジメトキシ、3・4−ジエトキシ、3・4−メチレンジオ
キシ、２−クロル、３−クロル、４−クロル、２−ブロ
モ、３−ブロモ、４−ブロモ、２−フルオロ、３−フル
オロ、４−フルオロ、２−ヨード、３−ヨード、４−ヨ
ードであるような５−（置換ベンジリデン）ヒダントイ
ンである。Specifically, 5- (benzylidene) hydantoin, or a group represented by R 1 and R 2 in the above general formula (I) is 2-hydroxy, 3-hydroxy, 4-hydroxy, 2,4-dihydroxy, 2.5-dihydroxy, 3.4-dihydroxy, 2-methyl, 3-methyl, 4-methyl, 2
-Ethyl, 3-ethyl, 4-ethyl, 2-propyl, 3
-Propyl, 4-propyl, 2-methoxy, 3-methoxy, 4-methoxy, 5-methyl-2-hydroxy, 3-
Methyl-4-hydroxy, 2-hydroxy-3-methoxy, 3-methoxy-4-hydroxy, 3-hydroxy-
4-methoxy, 2.4-dimethoxy, 3.4-dimethoxy, 3-
5-dimethoxy, 3,4-diethoxy, 3,4-methylenedioxy, 2-chloro, 3-chloro, 4-chloro, 2-bromo, 3-bromo, 4-bromo, 2-fluoro, 3-fluoro, 5- (substituted benzylidene) hydantoins such as 4-fluoro, 2-iodo, 3-iodo, 4-iodo.
これらの原料を用い、それぞれ対応する一般式（II） （式中、Ｒ1およびＲ2は一般式（Ｉ）の場合と同じ意味
を示す）で表わされるα−ケト酸が得られる。Using these raw materials, the corresponding general formula (II) An α-keto acid represented by the formula (wherein R 1 and R 2 have the same meaning as in the case of the general formula (I)) is obtained.
本発明の方法に使用されるアルカリ金属水酸化物には水
酸化ナトリウム、水酸化カリウム、水酸化リチウム等が
あり、そのアルカリとしての効果は同じであるが、水酸
化ナトリウムが最も安価であり経済的に好ましい。The alkali metal hydroxide used in the method of the present invention includes sodium hydroxide, potassium hydroxide, lithium hydroxide and the like, and the same effect as the alkali, but sodium hydroxide is the cheapest and economical. Is preferable.
アルカリ金属水酸化物の使用量は５−（置換アリ−リデ
ン）ヒダントインに対し1.5〜2.5モル倍の範囲であり、
1.5モル倍未満であると未反応の原料が多く残り、一
方、2.5モル倍を超えるとアルカリによるα−ケト酸の
分解が多くなり収率が急激に低下する。The amount of the alkali metal hydroxide used is in the range of 1.5 to 2.5 times the molar amount of 5- (substituted allylidene) hydantoin,
If it is less than 1.5 mol times, a large amount of unreacted raw material remains, while if it exceeds 2.5 mol times, the decomposition of α-keto acid by alkali increases and the yield decreases sharply.
反応温度は８０〜110℃、好ましくは９０〜105℃の範囲
が良い。８０℃未満では未反応５−（置換アリ−リデ
ン）ヒダントインが多くなり、110℃を超えると反応は
短時間に完結するが、同時に目的物の分解する割合が多
く、急激に収率が低くなる。これは生成したα−ケト酸
の熱安定生が極めて悪いためである。The reaction temperature is 80 to 110 ° C, preferably 90 to 105 ° C. When the temperature is lower than 80 ° C, the amount of unreacted 5- (substituted aryl-lidene) hydantoin increases, and when the temperature exceeds 110 ° C, the reaction is completed in a short time, but at the same time, the rate of decomposition of the target substance is high and the yield rapidly decreases. . This is because the α-keto acid produced has a very poor thermal stability.
反応時間は温度により多少変動するが、３〜５時間が良
く、長くなるとα−ケト酸の分解が起こり好ましくな
い。Although the reaction time varies somewhat depending on the temperature, it is good for 3 to 5 hours, and if it is long, the α-keto acid is decomposed, which is not preferable.
反応は、通常、水溶媒を用い、原料の５−（置換アリ−
リデン）ヒダントインを１〜２０wt％、好ましくは５〜
１５wt％の濃度で仕込み、反応を行うが、不活性な他の
有機溶媒を用いて行うことも可能である。The reaction is usually carried out using a water solvent, and the starting material 5- (substituted ally-
Redene) hydantoin 1 to 20 wt%, preferably 5 to
The reaction is carried out by charging at a concentration of 15 wt%, but it is also possible to carry out the reaction using another inert organic solvent.
また反応は常圧容器を用い大気圧下で行われるが、オー
トクレーブなどの耐圧容器で加圧下で行っても良い。The reaction is carried out under atmospheric pressure using a normal pressure vessel, but may be carried out under pressure in a pressure resistant vessel such as an autoclave.
生成したα−ケト酸のアルカリ塩を安定に存在させるた
めには、反応を窒素気流中で行うのが好ましい。The reaction is preferably carried out in a nitrogen stream in order to allow the produced alkali salt of α-keto acid to stably exist.
（作用および効果） 本発明の方法によれば、従来法で問題であったα−ケト
酸の低収率という欠点を一挙に解消し、しかも、アルカ
リ金属水酸化物及び中和用の鉱酸の使用量、ひいては、
多量の中和塩の副生を激減させることができる。(Operation and Effect) According to the method of the present invention, the disadvantage of low yield of α-keto acid, which has been a problem in the conventional method, is solved all at once, and moreover, an alkali metal hydroxide and a mineral acid for neutralization are used. The amount of
The by-product of a large amount of neutralized salt can be drastically reduced.
（実施例） 以下、本発明を更に実施例により説明する。(Examples) Hereinafter, the present invention will be described with reference to Examples.
実施例１ ５−（ベンジリデン）ヒダントイン15.0ｇ（0.08モ
ル）、苛性ソーダ6.6ｇ（0.16モル）とさらに水280ｇを
還流冷却器と温度計のついたガラス製反応器中に仕込
み、窒素気流下及び撹拌下103℃まで加熱し、その温度
にて３時間反応させた。Example 1 5- (Benzylidene) hydantoin 15.0 g (0.08 mol), caustic soda 6.6 g (0.16 mol) and further 280 g of water were charged into a glass reactor equipped with a reflux condenser and a thermometer, and under a nitrogen stream and stirring. The mixture was heated to 103 ° C below and reacted at that temperature for 3 hours.
反応後室温まで冷却し、反応液中の５−（ベンジリデ
ン）ヒダントイン及びフェニルピルビン酸の濃度を液体
クロマトグラフィーによって分析した結果、５−（ベン
ジリデン）ヒダントイン転化率99.5％、フェニルピルビ
ン酸収率96.7％を得た。融点155〜157℃。After the reaction, the mixture was cooled to room temperature, and the concentrations of 5- (benzylidene) hydantoin and phenylpyruvic acid in the reaction liquid were analyzed by liquid chromatography. As a result, the conversion rate of 5- (benzylidene) hydantoin was 99.5%, and the yield of phenylpyruvic acid was 96.7%. Got Melting point 155-157 ° C.
実施例２〜４及び比較例１〜３ 実施例１において苛性ソーダの量をかえる以外は全く同
じ条件で反応させた。その結果を表−１に示した。但
し、実施例４は原料使用量等の実験規模を３倍にして行
った。Examples 2 to 4 and Comparative Examples 1 to 3 In Example 1, the reaction was carried out under exactly the same conditions except that the amount of caustic soda was changed. The results are shown in Table-1. However, in Example 4, the experimental scale such as the amount of raw material used was tripled.
実施例５〜７及び比較例４、５ ５−（ベンジリデン）ヒダントイン、苛性ソーダと水の
各仕込量を実施例１と全く同じにし、窒素気流下、電磁
撹拌式オートクレーブに仕込み、表−２の各温度で撹拌
下３時間反応させた。その結果を表−２に示した。Examples 5 to 7 and Comparative Examples 4 and 55 5- (benzylidene) hydantoin, caustic soda and water were charged in exactly the same amounts as in Example 1, charged in a magnetic stirring autoclave under a nitrogen stream, and each of Table-2. The mixture was reacted at temperature for 3 hours with stirring. The results are shown in Table-2.
実施例８〜１１ 実施例１と同様の装置により、表−３に掲げた５−（置
換アリ−リデン）ヒダントインの0.08モルと苛性ソーダ
0.16モルと水280ｇを反応器に仕込み、撹拌下103℃で３
時間加水分解し、対応するα−ケト酸を得た。その結果
を表−３に示した。Examples 8 to 11 Using the same apparatus as in Example 1, 0.08 mol of 5- (substituted allylidene) hydantoin and caustic soda listed in Table 3 were used.
Charge 0.16 mol and 280 g of water into a reactor and stir at 103 ° C for 3
After hydrolysis for a period of time, the corresponding α-keto acid was obtained. The results are shown in Table-3.
フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 // Ｂ０１Ｊ 23/04 Ｘ 8017−4Ｇ Ｃ０７Ｂ 61/00 ３００ (56)参考文献 特開 昭53−46920（ＪＰ，Ａ) Ｃｈｅｍ．Ａｂｓｔｒ．88（１）：5826 ａContinuation of the front page (51) Int.Cl. 5 Identification number Reference number within the agency FI Technical display location // B01J 23/04 X 8017-4G C07B 61/00 300 (56) Reference JP-A-53-46920 (JP , A) Chem. Abstr. 88 (1): 5826 a
Claims (1)
基または炭素数１〜３のアルキル基を示し、互いに同一
または異ってもよい）で表わされる５−（置換アリ−リ
デン）ヒダントインを1.5〜2.5モル倍のアルカリ金属水
酸化物の存在下、８０〜110℃で加水分解することを特
徴とする一般式（II） （式中、Ｒ1およびＲ2は一般式（Ｉ）の場合と同じ意味
を示す。）で表わされるα−ケト酸の製造方法。1. A general formula (I) (In the formula, R 1 and R 2 represent a hydrogen atom, a halogen atom, a hydroxyl group or an alkyl group having 1 to 3 carbon atoms, and may be the same or different from each other.) 5- (substituted arylidene) hydantoin Is hydrolyzed at 80 to 110 ° C. in the presence of 1.5 to 2.5 molar times of alkali metal hydroxide. (In the formula, R 1 and R 2 have the same meanings as in the case of the general formula (I).) A method for producing an α-keto acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59141330A JPH0623130B2 (en) | 1984-07-10 | 1984-07-10 | Method for producing α-keto acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59141330A JPH0623130B2 (en) | 1984-07-10 | 1984-07-10 | Method for producing α-keto acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6122042A JPS6122042A (en) | 1986-01-30 |
| JPH0623130B2 true JPH0623130B2 (en) | 1994-03-30 |
Family
ID=15289433
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59141330A Expired - Lifetime JPH0623130B2 (en) | 1984-07-10 | 1984-07-10 | Method for producing α-keto acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0623130B2 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61167641A (en) * | 1985-01-21 | 1986-07-29 | Showa Denko Kk | Production of phenylpyruvic acid |
| US5216024A (en) * | 1987-07-28 | 1993-06-01 | Baylor College Of Medicine | Cell growth inhibitors and methods of treating cancer and cell proliferative diseases |
| WO2003014057A1 (en) * | 2001-08-08 | 2003-02-20 | Tanabe Seiyaku Co., Ltd. | Processes for producing halogenophenylpyruvic acid and optically active halogenophenylalanine |
| JP4838465B2 (en) * | 2001-09-28 | 2011-12-14 | 三菱レイヨン株式会社 | Process for producing 4-hydroxyphenylpyruvic acid |
| CN100412047C (en) * | 2005-12-15 | 2008-08-20 | 南京工业大学 | Method for quick preparation of phenyl pyruvic acid and its aryl substituted derivatives |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1096881A (en) * | 1976-10-07 | 1981-03-03 | Roger R. Gaudette | Preparation of aliphatic and heterocyclic alpha-keto carboxylic acids |
| JPS5488217A (en) * | 1977-12-20 | 1979-07-13 | Daiichi Kagaku Yakuhin Kk | Synthesis of alphaaketoisovaleric acid and salts thereof |
| JPS5495512A (en) * | 1978-01-10 | 1979-07-28 | Daiichi Kagaku Yakuhin Kk | Manufacture of alphaaketoisocaproic acid and its salts |
| JPS54103824A (en) * | 1978-02-03 | 1979-08-15 | Daiichi Kagaku Yakuhin Kk | Manufacture of alphaaketoobetaamethyllnn valeric acid and its salts |
-
1984
- 1984-07-10 JP JP59141330A patent/JPH0623130B2/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| Ｃｈｅｍ．Ａｂｓｔｒ．８８（１）：５８２６ａ |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6122042A (en) | 1986-01-30 |
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